Progression of symptoms in the early and middle stages of Huntington disease

Objective: To delineate the progression of symptoms in the early and middle stages of Huntington disease (HD). Design: A survey of individuals with symptomatic HD completed by a first-de gree relative. Setting: The National Huntington Disease Research Roster for Patients and F amilies, Indianapolis, Ind. Participants: The survey included 1238 individuals with a minimum of a 6-ye ar history of symptomatic HD. Measures: Participating families completed a series of surveys, including t he Affected Individual Questionnaire, which consists of 19 physical, emotio nal, and cognitive signs commonly thought to occur during disease progressi on. The respondent indicates if each of the symptoms occurred and, if so, a t what time during the course of the disease: (1) within 1 year, (2) within 2 to 5 years, (3) within 6 to 10 years, (4) after more than 10 years, (5) has not occurred, or (6) "don't know." Results: The symptoms are categorized into 6 onset periods. Involuntary mov ements are grouped alone as the earliest reported symptom. The second group is composed entirely of mental and emotional symptoms, including,sadness, depression, and difficult to get along with. The third group includes clums iness, sexual problems, lack of motivation, and suspiciousness/paranoia. As the disease progresses, a variety of motor, emotional/behavioral, and cogn itive symptoms are experienced, including unsteadiness, trouble holding ont o things, trouble walking, changes in sleeping patterns, delusions and hall ucinations, intellectual decline, and memory loss. With the approach of lat e-stage HD, affected individuals begin to experience speech difficulty and weight loss. In the late stage, patients lose bowel and bladder control. Conclusions: Even though the symptoms of HD are fairly well characterized, their progression, especially in the early and middle stages, remains uncer tain. Clarification of the disease progression is vital to improved underst anding of the pathogenesis of HD and to the evaluation of therapeutic agent s that are designed to slow the progression of disease. The results of this study assist in clarifying HD progression from early involuntary movements and emotional changes to more overt motor symptoms and difficulty with act ivities of daily living.